Marionette lines are cosmetic defects of the human face often caused by a loss of dermal collagen in the lower lips and chin area as a result of aging. These lines are usually accompanied by a downturn at the corners of the mouth, producing a “sad” appearance, hence the term “sad mouth”. In this condition, the horizontal symmetry of the mouth is offset in a downward or inferior direction as a result of the downturn at the corners of the mouth.
Some facial wrinkles and unsightly facial expressions are due to overactivity of the underlying facial musculature. Neuroparalytic toxins have been used for treatment of wrinkles and in other treatments for facial rejuvenation. A toxin capable of blocking neuromuscular activity is administered to a facial muscle responsible for the facial defect or lesion. Resulting paralysis of the facial muscle alleviates the facial defect. The preferred toxin for cosmetic use is Botulinum toxin (BTX).
BTX, produced by the bacterium Clostridium botulinum reversibly paralyzes striated muscle when administered in sub-lethal doses. BTX has been used in the treatment in a number of neuromuscular disorders and conditions involving muscular spasm including various forms of dystonia, hemifacial spasm, tremor, spasticity (e.g. resulting from Multiple sclerosis), anal fissures and various ophthalmologic conditions (c.f. A. Carruthers et al (1996), Botulinum A Exotoxin Use in Clinical Dermatology; Journal of the American Academy of Dermatology 34: 788-797).
BTX is a generic term covering a family of toxins produced by C. botulinum comprising up to eight serologically distinct forms (A, B, C1, C2, D, E, F and G). These toxins which are among the most powerful neuroparalytic agents known (c.f. Melling, J. et al (1988) Clostridium Botulinum: Nature and Preparation for Clinical Use; Eye 2: 16-23). Serotypes A, B and F are the most potent. The mode of action is to inhibit the release of acetylcholine by the presynaptic nerve.
BTX-A serotype is available commercially under the trademarks BOTOX™ (Allergan, Inc., Irvine, Calif. U.S.A.) and DYSPORT™ (Speywood Pharmaceuticals, Ltd., Maidenhead, U.K.). The initial cosmetic use of BTX was for treatment of forehead frown lines as reported in J. Carruthers and A. Carruthers (1992) “Treatment of Glabellar Frown Lines with C. Botulinum-A Exotoxin”; J. Dermatol. Surge Oncol. 18: 17-21. Subsequently, various facial treatments employing BTX have been reported but use of BTX for treatment of midfacial defects has been limited.
Application of BTX near the mouth has been limited to treatment of neuromuscular disorder. For example, hemifacial spasm has been treated by BTX injection to the zygomaticus muscle but the modeolus adjacent the corner of the mouth is avoided (J. Carruthers and A. Carruthers (1996) Botulinum A Exotoxin in Clinical Ophthalmology; Can. J. Ophthalmol. 31: 389-400).
It has been reported that BTX injection to a group of muscles on one side of a patient's face has been used to treat facial synkinesis and vertical asymmetry caused by facial nerve palsy (Armstrong, M. W. J. et al. (1996) “Treatment of Facial Synkinesis and Facial Asymmetry with Botulinum Toxin Type A Following Nerve Palsy”, Clin. Otolaryngol. 21:15-20). In the latter procedure, the levator anguli oris, zygomaticus major, rizorius and depressor anguli oris muscles associated with the mouth together with various muscles associated with the eye on the normal side of a patient's face were all treated as a group in order to affect the entire vertical symmetry of a patient's face to compensate for effects of nerve palsy on the untreated side of the face.
While BTX treatment of the platysma muscle has been performed for treatment of neck lines and banding, it has also been noted that injection of BTX into the platysma produces an uplift of the mouth (F. S. Brandt and B. Bellman (1998) Cosmetic Use of Botulinum A Exotoxin for the Aging Neck; Dermatol. Surg. 24: 1232-1234). Injection of BTX into the point of the chin has also been done for treatment of prominent mental crease (A. Carruthers and J. Carruthers; “Cosmetic Uses of Botulinum A Exotoxin”; In: James, W. D. et al Eds. Advances in Dermatology (1997) Mosby-Yearbook, Chicago: at pages 325-48).
The inventors have now found that “sad mouth” may be treated by simultaneous bilateral BTX injection to depressor anguli oris (triangularis) muscle (termed herein DAO) thereby affecting the horizontal symmetry of the mouth, without embarrassment to the appearance and function of the mouth. The normal function of the patient's lips is not impeded.